Atp8b1突变小鼠衰老肺脏的全基因表达谱分析

Global gene profiling of aging lungs in Atp8b1 mutant mice.

作者信息

Soundararajan Ramani, Stearns Timothy M, Czachor Alexander, Fukumoto Jutaro, Turn Christina, Westermann-Clark Emma, Breitzig Mason, Tan Lee, Lockey Richard F, King Benjamin L, Kolliputi Narasaiah

机构信息

Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.

MDI Biological Laboratory, Salisbury Cove, ME 04672, USA.

出版信息

Aging (Albany NY). 2016 Sep 29;8(9):2232-2252. doi: 10.18632/aging.101056.

OBJECTIVE

Recent studies implicate cardiolipin oxidation in several age-related diseases. encoding Type 4 P-type ATPases is a cardiolipin transporter. Mutation in gene or inflammation of the lungs impairs the capacity of Atp8b1 to clear cardiolipin from lung fluid. However, the link between mutation and age-related gene alteration is unknown. Therefore, we investigated how mutation alters age-related genes.

METHODS

We performed Affymetrix gene profiling of lungs isolated from young (7-9 wks, n=6) and aged (14 months, 14 M, n=6) C57BL/6 and mutant mice. In addition, Ingenuity Pathway Analysis (IPA) was performed. Differentially expressed genes were validated by quantitative real-time PCR (qRT-PCR).

RESULTS

Global transcriptome analysis revealed 532 differentially expressed genes in lungs, 157 differentially expressed genes in C57BL/6 lungs, and 37 overlapping genes. IPA of age-related genes in lungs showed enrichment of Xenobiotic metabolism and Nrf2-mediated signaling pathways. The increase in and transcripts in aged lungs was validated by qRT-PCR. Similarly, the decrease in and increase in transcripts was confirmed in both mutant and C57BL/6 lungs.

CONCLUSION

Based on transcriptome profiling, our study indicates that mutant mice may be susceptible to age-related lung diseases.

目的

近期研究表明心磷脂氧化与多种年龄相关疾病有关。编码4型P型ATP酶的是一种心磷脂转运蛋白。该基因突变或肺部炎症会损害Atp8b1从肺液中清除心磷脂的能力。然而，该基因突变与年龄相关基因改变之间的联系尚不清楚。因此，我们研究了该基因突变如何改变与年龄相关的基因。

方法

我们对从年轻（7 - 9周龄，n = 6）和老年（14个月，14M，n = 6）的C57BL/6和该基因突变小鼠分离的肺组织进行了Affymetrix基因芯片分析。此外，还进行了 Ingenuity Pathway Analysis（IPA）。差异表达基因通过定量实时PCR（qRT-PCR）进行验证。

结果

全转录组分析显示，该基因突变小鼠肺组织中有532个差异表达基因，C57BL/6小鼠肺组织中有157个差异表达基因，以及37个重叠基因。对该基因突变小鼠肺组织中与年龄相关基因的IPA分析表明，外源物代谢和Nrf2介导的信号通路富集。通过qRT-PCR验证了老年该基因突变小鼠肺组织中相关转录本的增加。同样，在该基因突变小鼠和C57BL/6小鼠的肺组织中均证实了相关转录本的减少和增加。